Organic polymers

ABSTRACT

The invention relates to novel crosslinkable copolymers of formula  
                 
 
     wherein the variables are as defined in the claims. The copolymers of the invention are especially useful for the manufacture of biomedical moldings, for example ophthalmic moldings such as in particular contact lenses.

[0001] The present invention relates to novel crosslinkable copolymers,to a process for the preparation thereof and to the use thereof for themanufacture of mouldings, especially ophthalmic mouldings.

[0002] U.S. Pat. Nos. 5,760,100 or 5,807,944 disclose crosslinkableamphiphilic block copolymers comprising a hydrophobic middle block towhich are linked two or more hydrophilic blocks. While the materialsdisclosed therein in general have proven to be effective as bulkmaterial for the manufacture of biomedical articles, the availability,chemical constitution and size of suitable hydrophilic blocks as well asthe further processing of the known block copolymers is oftenproblematic. In particular, the control of the segmental length of thehydrophilic segments is often difficult. Therefore, it would be highlydesirable to provide more easily accessible hydrophilic blocks ofvariable chain length having a single functional group undergoingcoupling with the hydrophobic segment and one or more differentfunctional groups useful to attach a polymerizable moiety. Suchhydrophilic blocks would allow to design specific crosslinkableamphiphilic block copolymers with specific polymer and segmentalarchitectures depending on the desired use. In addition, a simplifiedmanufacture of mouldings from such amphiphilic block copolymers would bedesirable which omits time consuming steps such as, for example, theremoval of extractables, that are unpolymerized components or compoundsthat are not firmly anchored in the polymer network, after thepolymerization or crosslinking step.

[0003] Therefore, it is an object of the invention to provide novelcrosslinkable amphiphilic block copolymers, within the application alsocalled prepolymers, which are based on easily accessible hydrophilicblocks with high variability of chemical constitution and segmenrallength, and which make it possible to manufacture mouldings, inparticular biomedical mouldings such as especially ophthalmic mouldings,in a very efficient manner.

[0004] The present invention therefore in one aspect relates to acrosslinkable amphiphilic block copolymer of formula

[0005] wherein A is a hydrophobic segment selected from the groupconsisting of a polysiloxane, a perfluoroalkyl polyether and mixturesthereof,

[0006] L is is a bivalent linking group of formula

-X₁-C(O)—NH-R-NH—C(O)-X₂-   (2a),

-X₁-C(O)-R-C(O)-X₂-   (2b),

—C(O)-X₂-   (2c),

-X₁-C(O)—  (2d)

[0007] or

-X₁-C(O)-X₂-   (2e),

[0008] wherein X₁ and X₂ are each independently of the other a group—O—, —S— or —NR₁-, R₁ is hydrogen or C₁-C₄-alkyl, R is linear orbranched C₁-C₁₈-alkylene or unsubstituted or C₁-C₄-alkyl- orC₁-C₄-alkoxy-substituted C₆-C₁₀-arylene, C₇-C₁₈-aralkylene,C₆-C₁₀-arylene-C₁-C₂-alkylene-C₆-C₁₀-arylene, C₃-C₈-cycloalkylene,C₃-C₈-cycloalkylene-C₁-C₆-alkylene,C₃-C₈-cycloalkylene-C₁-C₂-alkylene-C₃-C₈-cycloalkylene orC₁-C₆-alkylene-C₃-C₈-cycloalkylene-C₁-C6-alkylene; (alk) isC₂-C₁₂-alkylene;

[0009] (oligomer) is the radical of a hydrophilic telomer which isderived from one or more different copolymerizable vinyl monomers;

[0010] Q is an organic radical comprising at least one crosslinkable orpolymerizable group;

[0011] m is an integer from 1 to 4, and n is an integer≧1.

[0012] According to one preferred embodiment of the invention, thesegment A comprises a polysiloxane block having terminal alkylene groupsof formula

[0013] in which (alk′) is alkylene having up to 20 carbon atoms whichmay be interrupted by —O—; 80-100% of the radicals R₂, R₂′, R₂″, R₂′″,R₂*, R₃, R₃′ and R₃″, independently of one another, are C₁-C₈-alkyl and0-20% of the radicals R₂, R₂′, R₂″, R₂′″, R₂*, R₃, R₃′ and R₃″,independently of one another, are C₃-C₁₂-alkenyl, unsubsttituted orC₁-C₄ alkyl- or C₁-C₄- alkoxy-substituted phenyl, fluoro(C₁-C₁₈-alkyl)or cyano(C₁-C₁₂-alkyl), x is 0 or 1, d₁ is an integer of from 5 to 700,d₂ is (n−2) if x is 0, and is n if x is 1 wherein n is as defined above,and the sum of (d₁+d₂) is from 5 to 700.

[0014] In a preferred meaning, the sum of (d₁+d₂) is an integer from 10to 500, more preferably 10 to 300, particularly preferably 20 to 200 andin particular 25 to 150.

[0015] (alk′) is preferably C₂-C₈-alkylene, which may be interrupted by-0- and more preferably C₂-C₆-alkylene which may be interrupted by —O—.Examples of particular preferred radicals (alk′) are linear or branchedC₂-C₆ alkylene or a radical —(CH₂)₁₋₃—O—(CH₂)₁₋₃—, especiallyC₂-C₄-alkylene or a radical —(CH₂)₂₋₃—O—(CH₂)₂₋₃—.

[0016] Preferably the radicals R₂, R₂′, R₂″, R₂′″, R₂*, R₃, R₃′ and R₃″are each independently of one another C₁-C₆-alkyl, more preferably eachC₁-C₄-alkyl, more preferably each C₁-C₂-alkyl and in particular eachmethyl.

[0017] One embodiment of suitable polysiloxane hydrophobic blocks (A)emcompasses a radical of the above formula (3), wherein x is 0, d₂ is 0,d₁ is an integer from 5 to 700, preferably 10 to 500, more preferably 10to 300, even more preferably 20 to 200 and in particular preferably 25to 150, R₂, R₂′, R₂″, R₂′″, R₂*, R₃, R₃′ and R₃″ are each independentlyof one another C₁-C₆-alkyl, and for (alk′) the above given meanings andpreferences apply.

[0018] Another embodiment of suitable polysiloxane hydrophobic blocks(A) emcompasses a radical of the above formula (3), wherein x is 0, d₂is the sum of (n−2) and is≧1, and for R₂, R₂′, R₂″, R₂′″, R₂*, R₃, R₃′and R₃″,d₁ and (alk′) the above-given meanings and preferences eachapply.

[0019] Still another embodiment of suitable polysiloxane hydrophobicblocks (A) emcompasses a radical of the above formula (3), wherein x is1, d₂ is equivalent to n, and for R₂, R₂′, R₂″, R₂′″, R₂*, R₃, R₃′, d₁and R₃″ each the above-given meanings and preferences each apply.

[0020] According to another embodiment of the invention, theoxygen-permeable polymer in segment A comprises aperfluoroalkyl-polyether block of formula

-(E)_(k)-Z-CF₂—(OCF₂)_(b1)—(OCF₂CF₂)_(b2)—OCF₂-Z-(E)_(k)  (4)

[0021] in which (b1+b2) is a number in the range from 10 to 100; each Z,independently of the others, is a divalent radical having up to 12carbon atoms or a bond; each E, independently of the others, is alkoxy,e.g. —(OCH₂CH₂)_(a)—, where a has a value of from 0 to 2 as astatistical average, and where the link -Z-E- represents the sequence-Z-(OCH₂CH₂)_(a)—; and k is 0 or 1.

[0022] Z is preferably a bond, C₁-C₈-alkylene or —CONH-phenylene, inwhich the —CO— moiety is linked to a CF₂ group. Z is particularlypreferably C₁-C₄-alkylene, in particular methylene.

[0023] The perfluoroalkoxy units OCF₂ and OCF₂CF₂ having the indices b1and b2 in Formula (4) can have a random distribution. The sum of theindices (b1+b2) is preferably a number in the range from 10 to 50,particularly preferably from 10 to 30. The ratio b1:b2 is preferably inthe range from 0.5 to 1.5, in particular in the range from 0.8 to 1.2.

[0024] In one embodiment of the invention, the segment A may compriseone of the polymers illustrated above, in particular a polysiloxane.According to another embodiment, the polymer in segment A may comprisemore than one kind of polymers as illustrated above, e.g., may compriseperfluoroalkylene polyether subsegments and polysiloxane subsegments.

[0025] Segments A of the prepolymers of the invention have a meanmolecular weight of for example in the range from about 1,000 to about50,000, preferably in the range from about 1,500 to about 30000 andparticularly preferably in the range from about 2,000 to about 20,000.

[0026] The linking groups L of formulae (2a) - (2e) are to be understoodthat the left bond is directed to A and the right bond is directed to(alk).

[0027] If X₁ or X₂ is a group —NR₁-, R₁ is preferably methyl, ethyl orin particular hydrogen. X₁ and X₂ are each independently of the otherpreferably a group —O— or —NR₁- and more preferably —O— or —NH—.

[0028] R as alkylene in formula (2b) is preferably linear or branchedC₁-C₁₂-alkylene, more preferably C₁-C₆-alkylene and most preferablyC₁-C₄-alkylene.

[0029] R as alkylene in formula (2a) is preferably a linear or branchedC₃-C₁₄alkylene radical, more preferably a linear or branchedC₄-C₁₂alkylene radical and most preferably a linear or branchedC₆-C₁₀alkylene radical.

[0030] When R is arylene, it is, for example, naphthylene or especiallyphenylene, each of which may be substituted, for example, by C₁-C₄-alkylor by C₁-C₄-alkoxy. Preferably, R as arylene is 1,3- or 1,4-phenylenethat is unsubstituted or substituted by C₁-C₄-alkyl or by C₁-C₄-alkoxyin the ortho-position to at least one linkage site.

[0031] R as aralkylene is preferably naphthylalkylene and mostpreferably phenylalkylene. The alkylene group in aralkylene containspreferably from 1 to 12, more preferably from 1 to 6 and most preferablyfrom 1 to 4 carbon atoms. Most preferably, the alkylene group inaralkylene is methylene or ethylene.

[0032] When R is cycloalkylene, it is preferably C₅-C₆cycloalkylene andmost preferably cyclohexylene that is unsubstituted or substituted bymethyl.

[0033] When R is cycloalkylene-alkylene, it is preferablycyclopentylene-C₁-C₄-alkylene and especiallycyclohexylene-C₁-C₄-alkylene, each unsubstituted or mono- orpoly-substituted by C₁-C₄-alkyl, especially methyl. More preferably, thegroup cycloalkylene-alkylene is cyclohexylene-ethylene and, mostpreferably, cyclohexylene-methylene, each unsubstituted or substitutedin the cyclohexylene radical by from 1 to 3 methyl groups.

[0034] When R is alkylene-cycloalkylene-alkylene, it is preferablyC₁-C₄-alkylene-cyclopentylene-C₁-C₄-alkylene and especiallyC₁-C₄-alkylene-cyclohexylene-C₁-C₄-alkylene, each unsubstituted or mono-or poly-substituted by C₁-C₄-alkyl, especially methyl. More preferably,the group alkylene-cycloalkylene-alkylene isethylene-cyclohexylene-ethylene and, most preferably, ismethylene-cyclohexylene-methylene, each unsubstituted or substituted inthe cyclohexylene radical by from 1 to 3 methyl groups.

[0035] R as C₃-C₈-cycloalkylene-C₁-C₂-alkylene-C₃-C₈-cycloalkylene orC₆-C₁₀-arylene-C₁-C₂-alkylene-C₆-C₁₀-arylene is preferablyC₅-C₆-cycloalkylene-methylene-C₅-C₆-cycloalkylene orphenylene-methylene-phenylene, each of which may be unsubstituted orsubstituted in the cycloalkyl or phenyl ring by one or more methylgroups.

[0036] The radical R in formula (2a) has a symmetrical or, preferably,an asymmetrical structure.

[0037] L is preferably a radical of formula (2a). An especiallypreferred group of linking groups L comprises those of formula (2a),wherein R is linear or branched C₆-C₁₀alkylene; orcyclohexylene-methylene or cyclohexylene-methylene-cyclohexylene eachunsubstituted or substituted in the cyclohexyl moiety by from 1 to 3methyl groups.

[0038] Most preferably the bivalent radical R in formula (2a) is derivedfrom a diisocyanate and in particular from a diisocyanate selected fromthe group isophorone diisocyanate (IPDI), 4,4′-methylenebis (cyclohexylisocyanate), 1,6-diisocyanato-2,2,4-trimethyl-n-hexane (TMDI),methylenebis(cyclohexyl-4-isocyanate) and hexamethylene diisocyanate(HMDI).

[0039] Further suitable linking groups L comprise, for example, —C(O)O—,—OC(O)—, —C(O)NH— or —NHC(O)—.

[0040] The variable (alk) is preferably C₂-C₈-alkylene, more preferablyC₂-C₆-alkylene, even more preferably C₂-C₄-alkylene and particularlypreferably 1,2-ethylene. The alkylene radical (alk) may be branched orpreferably linear.

[0041] The variable m is, for example, a number from 1 to 4, preferablyfrom 1 to 3 and especially from 1 to2.

[0042] The telomer radical (oligomer)-(Q)_(m) corresponds, for example,to formula

[0043] wherein B and B′ are each independently of the other a1,2-ethylene radical derivable from a copolymerizable vinyl monomer thatis substituted by a hydrophilic substituent by replacing the vinylicdouble bond by a single bond,

[0044] B″ is a 1,2-ethylene radical derivable from a copolymerizablevinyl monomer by replacing the vinylic double bond by a single bond,

[0045] Q is an organic radical comprising at least one crosslinkable orpolymerizable group;

[0046] p and q are each independently of another an integer from 0 to150, wherein the total of (p+q) is an integer from 2 to 150,

[0047] u is, for example, an integer from 1 to 4, and

[0048] T is a monovalent group that is suitable to act as apolymerization chain-reaction terminator.

[0049] T is, for example, hydrogen.

[0050] Suitable hydrophilic substituents of the radicals B or B′ may benon-ionic, anionic, cationic or zwitterionic substituents. Accordingly,the telomer chain of formula (5) may be a charged chain containinganionic, cationic and/or zwitterionic groups or may be an unchargedchain. In addition, the telomer chain may comprise a copolymeric mixtureof uncharged and charged units. The distribution of the charges withinthe telomer, if present, may be random or blockwise.

[0051] In one preferrred embodiment of the invention, the telomerradical of formula (5) is composed solely of non-ionic monomer units Band optionally B′.

[0052] Suitable non-ionic substituents of B or B′ include for example aradical C₁-C₆-alkyl which is substituted by one or more same ordifferent substituents selected from the group consisting of —OH,C₁-C₄-alkoxy and —NR₄R₄′, wherein R₄ and R₄′ are each independently ofanother hydrogen or unsubstituted or hydroxy-substituted C₁-C₆-alkyl orphenyl; phenyl which is substituted by hydroxy, C₁-C₄-alkoxy or -NR₄R₄′,wherein R4 and R₄′ are as defined above; a radical —COOY, wherein Y isC₁-C₂₄-alkyl which is unsubstituted or substituted, for example, byhydroxy, C₁-C₄-alkoxy, —O—Si(CH₃)₃, —NR₄R₄′ wherein R₄ and R₄′ are asdefined above, a radical —O—(CH₂CH₂O)₁₋₂₄-R₉ wherein R₉ is hydrogen orC₁-C₆-alkyl, or a radical —NH—C(O)—O-G, wherein —O-G is the radical of asaccharide with 1 to 8 sugar units or is a radical —O—(CH₂CH₂O)₁₋₂₄-R₉,wherein R₉ is as defined above, or Y is C₅-C₈-cycloalkyl which isunsubstituted or substituted by C₁-C₄-alkyl or C₁-C₄-alkoxy, or isunsubstituted or C₁-C₄-alkyl- or C₁-C₄-alkoxy-substituted phenyl orC₇-C₁₂-aralkyl; —CONY₁Y₂ wherein Y₁ and Y₂ are each independentlyhydrogen, C₁-C₁₂-alkyl, which is unsubstituted or substituted forexample by hydroxy, C₁-C₄-alkoxy or a radical —O—(CH₂CH₂O)₁₋₂₄-R₉wherein R₉ is as defined above, or Y₁ and Y₂ together with the adjacentN-atom form a five- or six-membered heterocyclic ring having noadditional heteroatom or one additional oxygen or nitrogen atom; aradical —OY₃, wherein Y₃ is hydrogen; or C₁-C₁₂-alkyl which isunsubstituted or substituted by —NR₄R₄′; or is a radical—C(O)—C₁-C₄-alkyl; and wherein R₄ and R₄′ are as defined above; or afive- to seven-membered heterocyclic radical having at least one N-atomand being bound in each case via said nitrogen atom.

[0053] Suitable anionic substituents of B or B′ include for exampleC₁-C₆-alkyl which is substituted by —SO₃H, —OSO₃H, —OPO₃H₂ and —COOH;phenyl which is substituted by one or more same or differentsubstituents selected from the group consisting of —SO₃H, —COOH, —OH and—CH₂—SO₃H; —COOH; a radical —COOY₄, wherein Y₄ is C₁-C₂₄-alkyl which issubstituted for example by —COOH, —SO₃H, —OSO₃H, —OPO₃H₂ or by a radical—NH—C(O)—O-G′ wherein G′ is the radical of an anionic carbohydrate; aradical —CONY₅Y₆ wherein Y₅ is C₁-C₂₄-alkyl which is substituted by—COOH, —SO₃H, —OSO₃H, or —OPO₃H₂ and Y₆ independently has the meaning ofY₅ or is hydrogen or C₁-C₁₂-alkyl; or —SO₃H; each in form of the freeacid or in form of a salt, for example a sodium, potassium, ammonium orthe like salt thereof.

[0054] Suitable cationic substituents of B or B′ include C₁-C₁₂-alkylwhich is substituted by a radical —NR₄R₄′R₄″⁺An⁻, wherein R₄, R₄′ andR₄″ are each independently of another hydrogen or unsubstituted orhydroxy-substituted C₁-C₆-alkyl or phenyl, and An⁻ is an anion, forexample a biomedical acceptable anion such as a halide; or a radical—C(O)OY₇, wherein Y₇ is C₁-C₂₄-alkyl which is substituted by—NR₄R₄′R₄″⁺An⁻ and is further unsubstituted or substituted for exampleby hydroxy, wherein R₄, R₄′, R₄″ and An⁻ are as defined above.

[0055] Suitable zwitterionic substituents of B or B′ include a radical-R₁₀-Zw, wherein R₁₀ is a direct bond or a functional group, for examplea carbonyl, carbonate, amide, ester, dicarboanhydride, dicarboimide,urea or urethane group; and Zw is an aliphatic moiety comprising oneanionic and one cationic group each.

[0056] The following preferences apply to the hydrophilic substituentsof B and B′:

[0057] (i) non-ionic substituents:

[0058] Preferred alkyl substituents of B or B′ are C₁-C₄-alkyl, inparticular C₁-C₂-alkyl, which is substituted by one or more substituentsselected from the group consisting of —OH and —NR₄R₄′, wherein R₄ andR₄′ are each independently of another hydrogen or C₁-C₄-alkyl,preferably hydrogen, methyl or ethyl and particularly preferablyhydrogen or methyl, for example —CH₂—NH₂, —CH₂—N(CH₃)₂.

[0059] Preferred phenyl substituents of B or B′ are phenyl which issubstituted by —NH₂ or N(C₁-C₂-alkyl)₂, for example o-, m- orp-aminophenyl.

[0060] In case that the hydrophilic substituent of B or B′ is a radical—COOY, Y as optionally substituted alkyl is preferably C₁-C₆-alkyl, morepreferably C₁-C₄-alkyl, even more preferably C₁-C₃-alkyl andparticularly preferably methyl or ethyl, each of which beingunsubstituted or substituted as mentioned above. In case that the alkylradical Y is substituted by —NR₄R₄′, the above-given meanings andpreferences apply for R₄ and R₄′. Examples of suitable saccharidesubstituents —O-G of the alkyl radical Y that is substituted by—NH—C(O)—O-G are the radical of a mono- or disaccharide, for exampleglucose, acetyl glucose, methyl glucose, glucosamine, N-acetylglucosamine, glucono lactone, mannose, galactose, galactosamine,N-acetyl galactosamine, fructose, maltose, lactose, fucose, saccharoseor trehalose, the radical of an anhydrosaccharide such as levoglucosan,the radical of a glucosid such as octylglucosid, the radical of a sugaralcohol such as sorbitol, the radical of a sugar acid derivative such aslactobionic acid amide, or the radical of an oligosaccharide with amaximum of 8 sugar units, for example fragments of a cyclodextrin,starch, chitosan, maltotriose or maltohexaose. The radical —O-Gpreferably denotes the radical of a mono- or disaccharide or the radicalof a cyclodextrin fragment with a maximum of 8 sugar units. Particularpreferred saccharide radicals —O-G are the radical of trehalose or theradical of a cyclodextrin fragment. In case that the alkyl radical Y issubstituted by a radical —O—(CH₂CH₂O)₁₋₂₄-R₉ or —NH—C(O)—O-G wherein—O-G is —O—(CH₂CH₂O)₁₋₂₄-R₉, the number of (CH₂CH₂O) units is preferablyfrom 1 to 12 in each case and more preferably from 2 to 8. R₉ ispreferably C₁-C₂-alkyl or in particular hydrogen. Y as C₅-C₈-cycloalkylis for example cyclopentyl or preferably cyclohexyl, each of which beingunsubstituted or substituted for example by 1 to 3 C₁-C₂-alkyl groups.Yas C₇-C₁₂-aralkyl is for example benzyl.

[0061] Preferred nonionic radicals —COOY are those wherein Y isC₁-C₃-alkyl; or C₂-C₄-alkyl which is substituted by one or twosubstituents selected from the group consisting of hydroxy;;C₁-C₂-alkoxy; —O—Si(CH₃)₃; and —NR₄R₄′ wherein R₄ and R₄′ are eachindependently of another hydrogen or C₁-C₄-alkyl; or Y is a radical—CH₂CH₂—O—(CH₂CH₂O)₁₋₁₂—H; or is a radical —C₂-C₄-alkylene-NH—C(O)—O-G,wherein —O-G is the radical of a saccharide.

[0062] More preferred non-ionic radicals —COOY are those wherein Y isC₁-C₂-alkyl; or C₂-C₄-alkyl which is substituted by one or twosubstituents selected from the group consisting of —OH and —NR₄R₄′wherein R₄ and R₄′ are each independently of another hydrogen orC₁-C₂-alkyl; or a radical —CH₂CH₂—O—(CH₂CH₂O)₁₋₁₂—H; or is a radical—C₂-C₄-alkylene-NH—C(O)—O-G wherein —O-G is the radical of a saccharide.

[0063] Particularly preferred radicals —COOY comprise those wherein Y isC₁-C₂-alkyl, particularly methyl; or C₂-C₃-alkyl, which is unsubstitutedor substituted by hydroxy or N,N-di-C₁-C₂-alkylamino, or is a radical—CH₂CH₂—O—(CH₂CH₂O)₁₋₃—H or —C₂-C₃-alkylene-NH—C(O)—O-G wherein —O-G isthe radical of trehalose or the radical of a cyclodextrin fragment witha maximum of 8 sugar units.

[0064] Preferred non-ionic substituents —C(O)—NY₁Y₂ of B or B′ are thosewherein Y₁ and Y₂ are each independently of the other hydrogen orC₁-C₆-alkyl which is unsubstituted or substituted by hydroxy; or Y₁ andY₂ together with the adjacent N-atom form a heterocyclic 6-membered ringhaving no further heteroatom or having one further N- or O-atom. Evenmore preferred meanings of Y₁ and Y₂, independently of each other, arehydrogen or C₁-C₄-alkyl which is unsubstituted or substituted byhydroxy; or Y₁ and Y₂ together with the adjacent N-atom form aN-C₁-C₂-alkylpiperazino or morpholino ring. Particularly preferrednon-ionic radicals —C(O)—NY₁Y₂ are those wherein Y₁ and Y₂ are eachindependently of the other hydrogen, C₁-C₂-alkyl or hydroxy-C₁-C₂-alkyl;or Y₁ and Y₂ together with the adjacent N-atom form a morpholino ring.

[0065] Preferred non-ionic substituents —OY₃ of B or B′ are thosewherein Y₃ is hydrogen, C₁-C₄-alkyl which is unsubstituted orsubstituted by —NH₂ or —N(C₁-C₂-alkyl)₂, or is a group —C(O)C₁-C₂-alkyl.Y₃ is particularly preferred hydrogen or acetyl.

[0066] Preferred non-ionic heterocyclic substituents of B or B′ are a 5-or 6-membered heteroaromatic or heteroaliphatic radical having oneN-atom and in addition no further heteroatom or an additional N- or O-heteroatom, or is a 5 to 7-membered lactame. Examples of suchheterocyclic radicals are N-pyrrolidonyl, 2- or 4-pyridinyl, 2-methylpyridin-5-yl, 2-, 3- oder 4-hydroxypyridinyl, N-ε-caprolactamyl,N-imidazolyl, 2-methylimidazol-1-yl, N-morpholinyl or4-N-methylpiperazin-1-yl, particularly N-morpholinyl or N-pyrrolidonyl.

[0067] A group of preferred non-ionic substituents of B or B′ comprisesC₁-C₂-alkyl, which is substituted by —OH or —NR₄R₄′, wherein R₄ and R₄′are each independently of the other hydrogen or C₁-C₂-alkyl; a radical—COOY wherein Y is C₁-C₃-alkyl; C₂-C₄-alkyl which is substituted by —OH,—NR₄R₄′ wherein R₄ and R₄′ are each independently of another hydrogen orC₁-C₂-alkyl, or Y is a radical —CH₂CH₂—O—(CH₂CH₂O)₂₋₈—H or—C₂-C₄-alkylene-NH—C(O)—O-G wherein —O-G is the radical of a saccharide;a radical —C(O)—NY₁Y₂, wherein Y₁ and Y₂ are each independently of theother hydrogen or C₁-C₆-alkyl which is unsubstituted or substituted byhydroxy, or Y₁ and Y₂ together with the adjacent N-atom form aheterocyclic 6-membered ring having no further heteroatom or having onefurther N- or O-atom; a radical —OY₃, wherein Y₃ is hydrogen,C₁-C₄-alkyl which is unsubstituted or substituted by —NH₂ or—N(C₁-C₂-alkyl)₂, or is a group —C(O)C₁-C₂-alkyl; or a 5- or 6-memberedheteroaromatic or heteroaliphatic radical having one N-atom and inaddition no further heteroatom or an additional N-, O- or S-heteroatom,or a 5 to 7-membered lactame.

[0068] A group of more preferred non-ionic substituents of B or B′comprises a radical -COOY, wherein Y is C₁-C₂-alkyl, C₂-C₃-alkyl, whichis substituted by hydroxy, amino or N,N-di-C₁-C₂-alkylamino, or is aradical —CH₂CH₂—O—(CH₂CH₂O)₂₋₈—H or —C₂-C₄-alkylene-NH—C(O)—O-G wherein—O-G is the radical of trehalose or a cyclodextrin fragment with amaximum of 8 sugar units; a radical —CO—NY₁Y₂, wherein Y₁ and Y₂ areeach independently of the other hydrogen or C₁-C₄-alkyl which isunsubstituted or substituted by hydroxy, or Y₁ and Y₂ together with theadjacent N-atom form a N-C₁-C₂-alkylpiperazino or morpholino ring; or aheterocyclic radical selected from the group consisting ofN-pyrrolidonyl, 2- or 4-pyridinyl, 2-methylpyridin-5-yl, 2-, 3- oder4-hydroxypyridinyl, N-ε-caprolactamyl, N-imidazolyl,2-methylimidazol-1-yl, N-morpholinyl and 4-N-methylpiperazin-1-yl.

[0069] A particularly preferred group of non-ionic substituents of B orB′ comprises the radicals —COO—C₁-C₂-alkyl, —COO—(CH₂)₂₋₃—OH, —CONH₂,—CON(CH₃)₂, —CONH—(CH₂)₂—OH,

[0070] —COO(CH₂)₂₋₄—NHC(O)—O-G wherein —O-G is the radical of trehaloseor a cyclodextrin fragment with a maximum of 8 sugar units. Particularlypreferred non-ionic substituents of B and B′ are —CONH₂, —CON(CH₃)₂ or

[0071] (ii) anionic substituents:

[0072] Preferred anionic substituents of B or B′ are C₁-C₄-alkyl, inparticular C₁-C₂-alkyl, which is substituted by one or more substituentsselected from the group consisting of —SO₃H and —OPO₃H₂, for example—CH₂—SO₃H; phenyl which is substituted by —SO₃H or sulfomethyl, forexample o-, m- or p-sulfophenyl or o-, m- or p-sulfomethylphenyl; —COOH;a radical —COOY₄, wherein Y₄ is C₂-C₆-alkyl which is substituted by—COOH, —SO₃H, —OSO₃H, —OPO₃H₂, or by a radical —NH—C(O)—O-G′ wherein G′is the radical of lactobionic acid, hyaluronic acid or sialic acid, inparticular C₂-C₄-alkyl which is substituted by —SO₃H or —OSO₃H; aradical —CONY₅Y₆ wherein Y₅ is C₁-C₆-alkyl substituted by sulfo, inparticular C₂-C₄-alkyl substituted by sulfo, and Y₆ is hydrogen, forexample the radical —C(O)—NH—C(CH₃)₂—CH₂—SO₃H; or —SO₃H; or a suitablesalt thereof. Particular preferred anionic substituents of B or B′ are—COOH, —SO₃H, o-, m- or p-sulfophenyl, o-, m- or p-sulfomethylphenyl, aradical —CONY₅Y₆ wherein Y₅ is C₂-C₄-alkyl substituted by sulfo, and Y₆is hydrogen, or a biomedical acceptable salt thereof, for example asodium or ammonium salt.

[0073] (iii) cationic substituents:

[0074] Preferred cationic substituents of B or B′ are C₁-C₄-alkyl, inparticular C₁-C₂-alkyl, which is in each case substituted by—NR₉R₉′R₉″⁺An⁻; or a radical —C(O)OY₇ wherein Y₇ is C₂-C₆-alkyl, inparticular C₂-C₄-alkyl, which is in each case substituted by—NR₄R₄′R₄″⁺An⁻ and is further unsubstituted or substituted by hydroxy.R₄, R₄′ and R₄″ are each independently of another preferably hydrogen orC₁-C₄-alkyl, more preferably methyl or ethyl and particularly preferablymethyl. Examples of suitable anions An⁻ are Hal⁻, wherein Hal ishalogen, for example Br⁻, F⁻, J⁻ or particularly Cl⁻, furthermore HCO₃⁻, CO₃ ²⁻, H₂PO₃ ⁻, HPO₃ ²⁻, PO₃ ³⁻, HSO₄ ⁻, SO₄ ²⁻ or the radical of anorganic acid such as OCOCH₃ ⁻ and the like. A particularly preferredcationic substituent of B or B′ is a radical —C(O)OY₇ wherein Y₇ isC₂-C₄-alkyl, which is substituted by —N(C₁-C₂-alkyl)₃ ⁺An⁻ and isfurther substituted by hydroxy, and An⁻ is an anion, for example theradical —C(O)O—CH₂—CH(OH)—CH₂—N(CH₃)₃ ⁺An⁻.

[0075] (iv) zwitterionic substituents -R₁₀-Zw:

[0076] R₁₀ is a preferably a carbonyl, ester or amide functional groupand more preferably an ester group —C(O)—O—.

[0077] Suitable anionic groups of the moiety Zw are for example —COO⁻,—SO₃ ⁻, —OSO₃ ⁻, —OPO₃H⁻ or bivalent —O—PO₂ ⁻— or —O—PO₂ ⁻—O—,preferably a group —COO⁻ or —SO₃ ⁻ or a bivalent group —O—PO₂ ⁻—, and inparticular a group —SO₃ ⁻.

[0078] Suitable cationic groups of the moiety Zw are for example a group—NR₄R₄′R₄″⁺ or a bivalent group —NR₄R₄′⁺-, wherein R₄, R₄′ and R₄″ areas defined above, and are each independently of the other, preferablyhydrogen or C₁-C₆-alkyl, preferably hydrogen or C₁-C₄-alkyl and mostpreferably each methyl or ethyl.

[0079] The moiety Zw is for example C₂-C₃₀-alkyl, preferablyC₂-C₁₂-alkyl, and more preferably C₃-C₈-alkyl, which is in each caseuninterrupted or interrupted by —O— and substituted or interrupted byone of the above-mentioned anionic and cationic groups each, and, inaddition, is further unsubstituted or substituted by a radical —OY₈,wherein Y₈ is hydrogen or the acyl radical of a carboxylic acid.

[0080] Y₈ is preferably hydrogen or the acyl radical of a higher fattyacid.

[0081] Zw is preferably C₂-C₁₂-alkyl and even more preferablyC₃-C₈-alkyl which is substituted or interrupted by one of theabove-mentioned anionic and cationic groups each, and in addition may befurther substituted by a radical —OY₈.

[0082] A preferred group of zwitter-ionic substituents -R₃-Z correspondsto the formula

—C(O)O-(alk′″)-N(R₄)₂ ⁺-(alk′″)-An⁻

[0083] or

—C(O)O-(alk″)-O—PO₂ ⁻—(O)₀₋₁-(alk′″)-N(R₄)₃ ⁺

[0084] wherein R₉ is hydrogen or C₁-C₆-alkyl; An⁻ is an anionic group—COO—, —SO₃ ⁻, —OSO₃ ⁻ or —OPO₃H⁻, preferably —COO⁻ or —SO₃ ⁻ and mostpreferably —SO₃ ⁻, alk* is C₁-C₁₂-alkylene, (alk″) is C₂-C₂₄-alkylenewhich is unsubstituted or substituted by a radical —OY₈, Y₈ is hydrogenor the acyl radical of a carboxylic acid, and (alk′″) is C₂-C₈-alkylene.

[0085] (alk*) is preferably C₂-C₈-alkylene, more preferablyC₂-C₆-alkylene and most preferably C₂-C₄-alkylene. (alk″) is preferablyC₂-C₁₂-alkylene, more preferably C₂-C₆-alkylene and particularlypreferably C₂-C₃-alkylene which is in each case unsubstituted orsubstituted by hydroxy or by a radical —OY₈. (alk′″) is preferablyC₂-C₄-alkylene and more preferably C₂-C₃-alkylene. R₉ is hydrogen orC₁-C₄-alkyl, more preferably methyl or ethyl and particularly preferablymethyl. A preferred zwitterionic substituent of B or B′ is of formula

—C(O)O—CH₂—CH(OY₈)—CH₂—O—PO₂ ⁻—(CH₂)₂—N(CH₃)₃ ⁺,

[0086] wherein Y₈ is hydrogen or the acyl radical of a higher fattyacid.

[0087] B denotes for example a radical of formula

[0088] preferably a radical of formula (6a), wherein R₅ is hydrogen orC₁-C₄-alkyl, preferably hydrogen or methyl; R₆ is a hydrophilicsubstituent, wherein the above given meanings and preferences apply; R₇is C₁-C₄-alkyl, phenyl or a radical —C(O)OY₉, wherein Yg is hydrogen orunsubstituted or hydroxy-substituted C₁-C₄-alkyl; and R₈ is a radical—C(O)Y₉′ or —CH₂—C(O)OY₉ ¹ wherein Y₉ independently has the meaning ofYg.

[0089] R₇ is preferably C₁-C₂-alkyl, phenyl or a group —C(O)OY₉. R₈ ispreferably a group —C(O)OY₉′ or —CH₂—C(O)OY₉′ wherein Y₉ and Y₉′ areeach independently of the other hydrogen, C₁-C₂-alkyl orhydroxy-C₁-C₂-alkyl. Particularly preferred —CHR₇-CHR₈- units accordingto the invention are those wherein R₇ is methyl or a group —C(O)OY₉ andR₈ is a group —C(O)OY₉′ or —CH₂—C(O)OY₉′ wherein Y₉ and Y₉′ are eachhydrogen, C₁-C₂-alkyl or hydroxy-C₁-C₂-alkyl.

[0090] B′ independently may have one of the meanings given above for B.

[0091] The crosslinkable or polymerizable group contained in Q ispreferably an ethylenically unsaturated C—C double bond. A suitablesubstituent Q of the radical (oligomer) or B″ is, for example, a radicalof the formula

(R₁₁)_(t)-X-Q₁  (7),

[0092] wherein R₁₁ is C₁-C₈-alkylene or a radical of formula

—C(O)-X₃-Alk-  (8a),

—C(O)—O-Alk′-NH—C(O)—O—(CH₂CH₂₀)₉—CH₂CH₂—,  (8b)

[0093] or

—C(O)—O-Alk′-NH—C(O)—O-G₁-  (8c),

[0094] Alk is C₂-C₁₂-alkylene which is unsubstituted or substituted, forexample, by hydroxy or a radical —N(R₁₂)₃ ⁺An- wherein R₁₂ is hydrogenor C₁-C₄-alkyl and An⁻ is an anion, Alk′ is C₂-C₁₂-alkylene, X₃ is —O—or —NR₁₃-, R₁₃ is hydrogen or C₁-C₄-alkyl, t is an integer of 0 or 1, gis an integer from 1 to 23, G₁ independently has the meaning of thesaccharide radical G reduced by one hydroxy group; X is a group —O—,—S—, —NR₁₃′- or —N(R₁₃′)₂ ⁺-An⁻ wherein R₁₃′ is hydrogen or C₁-C₄-alkyland An⁻ is an anion, Q₁ is, for example, a radical R₁₄ as defined belowor is a radical of formula

[0095] (Alk″) is linear or branched C₃-C₆-alkylene, (Alk*) is linear orbranched C₁-C₆-alkylene, (Alk**) is linear or branched C₂-C₁₂-alkylene,and

[0096] R₁₄ is, for example, a radical of formula

[0097] wherein R₁₇ is hydrogen, C₁-C₄-alkyl or halogen, and each of R₁₅and R₁₆ independently of the other is hydrogen, C₁-C₄-alkyl, phenyl,carboxy or halogen. R₁₁ as alkylene is preferably methylene. If R₁₁ is aradical of formula (8a), (Alk) is preferably C₂-C₆-alkylene, morepreferably C₂-C₄-alkylene and in particular ethylene; and X₃ ispreferably —NH—, —N(C₁-C₂-alkyl)- or —O—, in particular —NH— or—N(C₁-C₂-alkyl)-. If R₁₁ is a radical of formula (8b), (Alk′) ispreferably C₂-C₆-alkylene, more preferably C₂-C₄-alkylene and inparticular ethylene; and g is preferably an integer of from 1 to 12 andespecially from 2 to 8. If R₁₁ is a radical of formula (8c), for (Alk′)the above given preferences apply; and —OG₁ is preferably the radical oftrehalose or a cyclodextrin fragment with a maximum of 8 sugar unitseach reduced by one hydroxy group.

[0098] R₁₁ is preferably a radical of formula (8a). The variable t ispreferably the number 1. X is preferably —O— or —NH—, in particular —O—.

[0099] R₁₇ is preferably hydrogen, methyl or chlorine and mostpreferably hydrogen or methyl. Each of R₁₅ and R₁₆ independently of theother is preferably hydrogen, carboxy, chlorine, methyl or phenyl. In apreferred embodiment of the invention, R₁₅ is hydrogen or methyl and R₁₆is hydrogen or carboxy. Most preferably, R₁₅ and R₁₆ are each hydrogen.

[0100] Examples of suitable radicals R₁₄ are vinylcarbonyl,1-methylvinylcarbonyl, styrylcarbonyl, 2-carboxyvinylcarbonyl,2-chloro-2-carboxyvinylcarbonyl, 1,2-dichloro-2-carboxyvinylcarbonyl,1,2-dimethyl-2-carboxyvinylcarbonyl and 2-methyl-2-carboxyvinylcarbonyl.

[0101] Especially preferred radicals R₁₄ correspond to formula (10)wherein R₁₇ is hydrogen or methyl, R₁₅ is carboxy or particularlyhydrogen, and R₁₆ is hydrogen, methyl, chlorine or phenyl, in particularhydrogen.

[0102] The radical -[(Alk″)-OH]— in formula (9a) is preferably2-hydroxy-1,3-propylene. (Alk*) is preferably C₁-C₃-alkylene, forexample methylene or in particular 1,1-dimethylmethylene. (Alk**) ispreferably C₂-C₆-alkylene, more preferably C₂-C₄-alkylene and inparticular ethylene. Q₁ is preferably a radical R₁₄ of formula (10) or aradical of formulae (9b) or (9c), in particular a radical of formula(9c).

[0103] Especially preferred radicals -Q₁ correspond to formula

[0104] A suitable moiety [B″-Q] in formula (5) corresponds, for example,to formula

[0105] wherein R₅″ is hydrogen or C₁-C₄-alkyl, preferably hydrogen ormethyl, and for Q₁, X, R₁₁ and t each the above given meanings andpreferences apply. An especially preferred moiety [B″-Q] of formula (5)corresponds to the formula (6c) above, wherein t is 1, R₁₁ is a radicalof the formula (8a) above, preferably a radical—CON(C₁-C₂-alkyl)-CH₂—CH₂— or —CONH—CH₂—CH₂—, X is —O—, and Q₁ is aradical

[0106] The total of (p+q) is, for example, an integer from 2 to 150,more preferably from 5 to 100, even more preferably from 5 to 75 andparticularly preferably from 10 to 50. u is preferably a number from 1to 3, and especially from 1 to 2. In one preferred embodiment of theinvention u is a number from 1 to 2, q is 0, and p is an integer from 1to 149, preferably from 3 to 99, more preferably from 4 to 74 andparticularly preferably from 9 to 49. In another preferred embodiment ofthe invention u is a number from 1 to 2 , p and q are each independentlyan integer of≧1 and the sum of (p+q) is an integer from 2 to 149,preferably from 3 to 99, more preferably from 4 to 74 and especiallyfrom 9 to 49.

[0107] The hydrophilic blocks, for example, of formula (5) have anweight average molecular weight of, for example, 200 to 20000,preferably 250 to 12500, more preferably from 350 to 5000, and inparticular 500 to 2500.

[0108] The variable n in formula (1) is for example an integer from 1 to20, preferably from 1 to 10, more preferably from 2 to 8 and even morepreferably from 2 to 6. One especially preferred embodiment of theinvention relates to block copolymers of formula (1), wherein n is thenumber 2. Another embodiment relates to block copolymers of formula (1),wherein n is an integer from 3 to 8 and in particular 4 to 6.

[0109] The structure of the crosslinkable copolymers of the inventionmay vary within wide limits. They may thus consist in one embodiment ofone segment A and one segment -[L-(alk)-S-(oligomer)-(Q)_(m)] only(diblock copolymers), or of one segment A and two segments-(alk)-S-(oligomer)-(Q)_(m) linked to its termini by the linking group L(triblock copolymers, or may have a comb-type structure wherein severalfragments -[L-(alk)-S-(oligomer)-(Q)_(m)] are pendent from one segment A(comb-block copolymers), wherein A, L, (alk), (oligomer) and (Q)_(m)each have the above-given meaning.

[0110] Formulae (3), (4) and (5) are to be understood as a statisticdescription of the respective compounds and radicals, that is to say theorientation and sequence of the units are not fixed in anyway by saidformulae. In addition, the value of m or u in formulae (1) and (1a) is astatistically one which indicates that for a given number of n segments-[L-(alk)-S-(oligomer)] within a copolymer of formula (1) each of saidsegments statistically comprises m or u units Q or Q₁.

[0111] One group of preferred amphiphilic block copolymers of theinvention are triblock copolymers of formula

[0112] wherein R₅′ independently has the meaning of R₅, R₆′independently has the meaning of R₆, n is 2, and for A, L, (alk), R₅,R₅″, R₆, R₆′, R₁₁, X, Q₁, T, p, q, u and t each the above given meaningsand preferences apply.

[0113] The block copolymers of formula (1) may be prepared by methodsknown per se. For example, in a first step there is provided a compoundof formula

[0114] wherein A, L, (alk), (oligomer), R₁₁, X, n und t each have theabove given meaning and m1 is an integer of ≧1, for example an integerfrom 1 to 150,

[0115] which is then reacted with about (n•m) molar equivalents of, forexample, a compound of formula

R₁₄-O-(Alk**)-N═C═O  (12e)

[0116] wherein Hal is halogen, in particular bromine or chlorine, R₁₄′has the meaning of R₁₄ reduced by the carbonyl group, and R₁₄, (Alk*)and (Alk**) are each as defined above.

[0117] Preferably, the oligomer portion of the compound of formula (11)is a homopolymer or copolymer derived from one or two hydrophilicethylenically unsaturated monomers, wherein at least one of saidmonomers comprises a functional group that is coreactive with acarboxylic acid halide, carboxylic acid anhydride, epoxy, lactone,aziactone or isocyanato group, and which is endcapped in part with acompound, for example, of formula (12a), (12b), (12c), (12d) or (12e).

[0118] The reactions of a compound of formula (12a)-(12e) having acarboxylic acid halide group, carboxylic acid anhydride group, epoxygroup, azlactone group or isocyanato group with an thiol, amino orhydroxy compound of formula (11) are well-known in the art and may becarried out as desribed in textbooks of organic chemistry.

[0119] For example, the reaction of the carboxylic acid halide offormula (12a) with a compound of formula (11) can be carried out underthe conditions that are customary for ester, thioester, or amideformation, for example at temperatures of, for example, from −40 to 80°C., preferably from 0 to 50° C. and most preferably from 0 to 25° C., ina dipolar aprotic solvent, e.g. tetrahydrofuran, dioxane, DMSO or anaprotic solvent as mentioned below, or in a mixture of water and one ofthe mentioned solvents, in the presence of a base, e.g. an alkali metalhydroxide, and, where applicable, in the presence of a stabiliser.Suitable stabilisers are, for example, 2,6-dialkylphenols, hydroquinonederivatives, e.g. hydroquinone or hydroquinone monoalkyl ethers, orN-oxides, e.g. 4-hydroxy-2,2,6,6-tetramethyl-piperidin-1-yl. Thereaction times may vary within wide limits, a period of, for example,from 30 minutes to 12 hours, preferably from 1 to 6 hours and especiallyfrom 2 to 3 hours, generally having been found practicable.

[0120] The reaction of a carboxylic acid anhydride or epoxide of formula(12b) or (12c) with a compound of formula (11) may be carried out asdescribed in organic textbooks, for example in an acidic or in a basicmedium.

[0121] The reaction of an azlactone of formula (12d) with a compound offormula (11) may be carried out at elevated temperature, for example atabout 50 to 75° C., in a suitable organic solvent, for example anaprotic polar solvent such as DMF, DMSO, dioxane and the like,optionally in the presence of a catalyst, for example in the presence ofa tertiary amine such as triethyl amine or an organotin salt such asdibutyltin dilaurate, or in particular in the presence of1,8-diazabicyclo[5.4.0]undec-7-ene (DBU).

[0122] The reaction of a compound of formula (12e) with a compound offormula (11) can be carried out under the conditions that are customaryfor the formation of urethanes or ureas. In case of urethane formationit is advantageously to perform the reaction in an inert solvent. Aminesof the formula (11) may be reacted with the isocyanate of formula (12e)also in an aqueous medium.

[0123] Suitable inert solvents for the reaction of a compound of formula(11) with a compound of formula (12e) are aprotic, preferably polar,solvents, for example hydrocarbons (petroleum ether, methylcyclohexane,benzene, toluene, xylene), halogenated hydrocarbons (chloroform,methylene chloride, trichloroethane, tetrachloroethane, chlorobenzene),ethers (diethyl ether, dibutyl ether, ethylene glycol dimethyl ether,diethylene glycol dimethyl ether, tetrahydrofuran, dioxane), ketones(acetone, dibutyl ketone, methyl ethyl ketone, methyl isobutyl ketone),carboxylic acid esters and lactones (ethyl acetate, butyrolactone,valerolactone), alkylated carboxylic acid amides (N,N-dimethylacetamide,N-methylpyrrolidone), nitriles (acetonitrile), sulfones and sulfoxides(dimethyl sulfoxide, tetramethylenesulfone). Polar solvents arepreferably used. The reaction temperature may be, for example, from −40to 200° C. When catalysts are used, the temperatures may advantageouslybe in the range of from 0 to 50° C., preferably at room temperature.Suitable catalysts are, for example, metal salts, such as ferricchloride or alkali metal salts of carboxylic acids, tertiary amines, forexample (C₁-C₆alkyl)₃N (tri-ethylamine, tri-n-butylamine),N-methylpyrrolidine, N-methylmorpholine, N,N-dimethylpiperidine,pyridine and 1,4-diaza-bicyclooctane. Tin salts have been found to beespecially effective, especially alkyltin salts of carboxylic acids, forexample dibutyltin dilaurate and tin dioctoate. The isolation andpurification of the compounds prepared is carried out according to knownmethods, for example by means of extraction, crystallisation,recrystallisation or chromatographic purification methods.

[0124] The compounds of the formula (12a), (12b), (12c), (12d) and (12e)are known compounds which are commercially available or may be preparedaccording to known methods.

[0125] The compounds of formula (11) are novel and represent a furtherobject of the invention. They may be prepared by methods known per se.For example the block copolymers of formula (1) having a linking groupof formula of formula (2a) or (2b) may be prepared by reacting in anyorder a compound of formula

A-(X₁H)_(n)  (13),

[0126] about n molar equivalents of a compound of formula

X*-R-X*  (14),

[0127] and about molar equivalents of a compound of formula

[0128] wherein X* is a group —N═C═O or carboxy or a suitable derivativethereof, for example a group —C(O)OH, —C(O)OR₂₀ or —C(O)—OHal whereinR₂₀ is, for example, C₁-C₄-alkyl, phenyl or benzyl and Hal is halogen,in particular bromine or chlorine, and A, R, R₁₁ X, X₁, X₂, (alk),(oligomer), n, m1 and t are each as defined above.

[0129] For example, the compound of formula (13) may be first reactedwith about one molar equivalent of a compound of formula (14), and theintermediate obtained is then reacted with the compound of formula (15).Another synthetic route comprises first reacting a compound of formula(15) with a compound of formula (14), and the intermediate obtained isthen reacted with a compound of formula (13). The reactions can becarried out under the conditions that are customary for ester,thioester, amide, urethane or urea formation, for example as outlinedabove.

[0130] The amphiphilic block copolymers of the invention wherein L is alinking group of formulae (2c) or (2d) may be prepared , for example, byreacting a compound of the formula

A-(X**)_(n)  (13a)

[0131] with about n molar equivalents of a compound of the above formula(15), or by reacting a compound of the above formula (13) with about nmolar equivalents of a compound of formula

[0132] wherein X** is carboxy or a suitable derivative thereof, forexample a group —C(O)OH, —C(O)OR₂₀ or —C(O)—OHal, and R, R₁₁, R₂₀ X,Hal, (alk), (oligomer), n, m1 and t each have the above-mentionedmeaning.

[0133] The reaction of the components of formulae (13a) and (15) or (13)and (15a), respectively, can be carried out under the conditions thatare customary for ester, thioester or amide formation, for example asoutlined above.

[0134] The amphiphilic block copolymers of the invention wherein L is alinking group of formulae (2e) may be prepared, for example, by reactinga compound each of the formula (13) and (15) with phosgene.

[0135] The compounds of formulae (13), (13a) and (14) are known or maybe obtained according to methods known in the art. Likewise, thehydrophilic telomers of formula (15) or (15a) may be prepared accordingto known processes, for example, according to PCT application WO92/09639, by copolymerizing one or more hydrophilic ethylenicallyunsaturated monomers in the presence of a functional chain transferagent wherein at least one monomer of the copolymerization mixture iscapable afterwards to fix a crosslinkable or polymerizable moiety Q. Thecompounds of formula

[0136] wherein X₄ is —SH, —NHR₁, carboxy or a carboxy derivative, forexample a group —C(O)OH, —C(O)OR₂₀ or —C(O)—OHal, wherein R₁, R₂₀ andHal are as defined above, and is preferably —NH₂ or —NH(C₁-C₂-alkyl),and for (alk), B, B′, B″, T, p, q, t, u, R₁₁ and X each the above givenmeanings and preferences apply, are novel and represent a further objectof the invention.

[0137] A process for the preparation of the preferred compounds offormula (15) or (15a) comprises copolymerizing a mixture comprising

[0138] p molar equivalents of a compound of formula

[0139] q molar equivalents of a compound of formula

[0140] u equivalents of a compound of formula

[0141] in the presence of a chain transfer agent of formula

HX′-(alk)-SH  (18)

[0142] and optionally in the presence of an initiator for radicalpolymerization, wherein X′ has the meaning of -X₂H or X** above, and R₅,R₅′, R₅″, R₆, R₆′, R₁₁, X and t each have the above given meaning.

[0143] Since the compounds of formulae (16) and (17) may be identical, aparticularly preferred process for the preparation of the compounds offormula (15) or (15a) comprises homo- or copolymerizing (p+u)equivalents of a monomer of formula (17) and optionally q equivalents ofa monomer of formula (16a).

[0144] The radical polymerization of the monomer mixture may be inducedphotochemically or preferably thermally. Suitable thermal polymerizationinitiators are known to the skilled artisan and comprise, for exampleperoxides, hydroperoxides, azo-bis(alkyl- or cycloalkylnitriles),persulfates, percarbonates or mixtures thereof. Examples arebenzoylperoxide, tert.-butyl peroxide, di-tert.-butyl-diperoxyphthalate,tert.-butyl hydroperoxide, azo-bis(isobutyronitrile),1,1-azodiisobutyramidine, 1,1′-azo-bis (1-cyclohexanecarbonitrile),2,2′-azo-bis(2,4-dimethyl-valeronitrile) and the like. Examples ofsuitable chain transfer agents of formula (18) are cysteamine (usuallyintroduced as hydrochloride) or thioglycolic acid. The polymerization iscarried out conveniently in an aqueous medium, preferably in an acidicmedium which has a pH of from 2 to 6 and preferably 3 to 5, such asaqueous acetic acid or deluted hydrochloric acid, at elevatedtemperature, for example at a temperature of from 25 to 100° C. andpreferably 40 to 80° C. The resulting telomer mixtures may be worked upin conventional manner using for example extraction, precipitation,ultrafiltration and the like techniques.

[0145] The hydrophilic blocks -[L-(alk)-S-(oligomer)-(Q)_(m)] of theblock copolymers of the invention have an weight average molecularweight of, for example, from 200 to 20000, preferably from 250 to 12500,more preferably from 350 to 5000, and in particular from 500 to 2500.

[0146] The molecular weight of the copolymers of the formula (1) is,within wide limits, not critical. Preferably, however, the prepolymerhas a weight average molecular weight of from approximately 1400 to200000, preferably from 2000 to 100000 and more preferably from 2500 to50000 and most preferably from 3000 to 25000.

[0147] The amphiphilic block copolymers formula (1) are prepolymers andare therefore crosslinkable, but uncrosslinked or, at least,substantially uncrosslinked; in addition, they are stable, that is tosay spontaneous crosslinking as a result of homopolymerisation does nottake place.

[0148] The prepolymers of formula (1) according to the invention arecrosslinkable in a controlled and extremely effective manner, especiallyby photo-crosslinking.

[0149] The present invention further relates, therefore, to a polymerthat can be obtained by photo-crosslinking of a prepolymer of formula(1), in the presence or, preferably, in the absence of an additionalvinyl comonomer. These crosslinked polymers are water-insoluble.

[0150] In the photo-crosslinking, a photoinitiator capable of initiatingfree-radical crosslinking is suitably added. Examples thereof will befamiliar to the person skilled in the art, suitable photoinitiators thatmay specifically be mentioned being benzoin methyl ether,1-hydroxycyclohexylphenyl ketone, Darocure 1173 or Irgacure types. Thecrosslinking can then be brought about by actinic radiation, e.g. UVlight, or ionising radiation, e.g. gamma rays or X-rays. The amount ofphotoinitiator may be selected within wide limits, an amount of up to0.05 g/g of polymer and especially of up to 0.003 g/g of polymer havingproved beneficial.

[0151] The crosslinkable copolymer of formula (1) is introduced into thecrosslinking process preferably in pure form, particularly substantiallyfree from undesired constituents, such as, for example, free frommonomeric, oligomeric or polymeric starting compounds used for thepreparation of the prepolymer, and/or free from secondary productsformed during the preparation of the prepolymer. Said prepolymers inpure form are obtained advantageously by previously purifying them in amanner known per se, for example by precipitation with a suitablesolvent, filtration and washing, extraction in a suitable solvent,dialysis, reverse osmoses (RO) or ultrafiltration, reverse osmoses andultrafiltration being especially preferred.

[0152] The preferred purification processes for the prepolymers of theinvention, reverse osmoses and ultrafiltration, can be carried out in amanner known per se. It is possible for the ultrafiltration and reverseosmoses to be carried out repeatedly, for example from two to ten times.Alternatively, the ultrafiltration and reverse osmoses can be carriedout continuously until the selected degree of purity is attained. Theselected degree of purity can in principle be as high as desired.

[0153] The copolymers of formula (1) may be crosslinked, for example, inform of a solution or a mesophase.

[0154] One embodiment of the invention relates to thephoto-polymerisation of the block copolymers of the invention insolution, preferably in one or more different organic solvents. Suitablesolvents are in principle all solvents that dissolve the polymersaccording to the invention and an optional vinyl comonomer which may beadditionally used, e.g. alcohols, such as C₁-C₆- alkanols, e.g. n- oriso-propanol, ethanol or methanol, glycols such as ethylene glycol,diethylene glycol, propylene glycol, butylene glycol, carboxylic acidamides, such as dimethylformamide, or dimethyl sulfoxide, and mixturesof suitable solvents, e.g. mixtures of water with an alcohol, e.g. awater/propanol, water/ethanol or a water/methanol mixture, or mixturesof water with a glycol.

[0155] According to this embodiment of the invention, thephoto-crosslinking is preferably effected from a solution comprising (i)one or more prepolymers according to the invention which can be obtainedas a result of the preferred purification step, ultrafiltration, (ii)one or more solvents selected from the group consisting of a C₁-C₆-alkanol, a glycol, a carboxylic acid amide, dimethyl sulfoxide andwater, and optionally (iii) an additional vinyl comonomer. For example,photo-crosslinking of the prepolymers is carried out in ethanol or n- oriso-propanol.

[0156] The vinyl comonomer that can additionally be used according tothe invention in the photo-crosslinking may be hydrophilic orhydrophobic or may be a mixture of a hydrophobic and a hydrophilic vinylmonomer. Suitable vinyl monomers include especially those which arecustomarily used in the manufacture of contact lenses. The expression“hydrophilic vinyl monomer” is understood to mean a monomer thattypically produces as homopolymer a polymer that is water-soluble orcapable of absorbing at least 10% by weight water. Analogously, theexpression “hydrophobic vinyl monomer” is understood to mean a monomerthat typically produces as homopolymer a polymer that is water-insolubleor capable of absorbing less than 10% by weight water.

[0157] The proportion of vinyl comonomers, if used, is preferably from0.5 to 80 units per prepolymer of formula (1), especially from 1 to 30units of vinyl comonomer per prepolymer unit of formula (1) and mostpreferably from 5 to 20 units per prepolymer of formula (1).

[0158] It is also preferred to use a hydrophobic vinyl comonomer or amixture of a hydrophobic vinyl comonomer with a hydrophilic vinylcomonomer, the mixture containing at least 50% by weight of ahydrophobic vinyl comonomer. In that manner, the mechanical propertiesof the polymer can be improved without the water content beingappreciably reduced. In principle, however, both conventionalhydrophobic vinyl comonomers and conventional hydrophilic vinylcomonomers are suitable for copolymerisation with a prepolymer offormula (1).

[0159] Suitable hydrophobic vinyl comonomers include, without thefollowing being an exhaustive list, C₁-C₁₈alkyl acrylates andmethacrylates, C₃-C₁₈alkylacrylamides and -methacrylamides,acrylonitrile, methacrylonitrile, vinyl-C₁-C₁₈alkanoates, C₂-C₁₈alkenes,C₂-C₁₈haloalkenes, styrene, C₁-C₆alkylstyrene, vinyl alkyl ethers inwhich the alkyl moiety has from 1 to 6 carbon atoms,C₂-C₁₀perfluoroalkyl acrylates and methacrylates or correspondinglypartially fluorinated acrylates and methacrylates,C₃-C₁₂perfluoroalkyl-ethyl-thiocarbonylaminoethyl acrylates andmethacrylates, acryloxy- and methacryloxy-alkylsiloxanes,N-vinylcarbazole, C₁-C₁₂alkyl esters of maleic acid, fumaric acid,itaconic acid, mesaconic acid and the like. Preferred are, for example,C₁-C₄alkyl esters of vinylically unsaturated carboxylic acids havingfrom 3 to 5 carbon atoms or vinyl esters of carboxylic acids having upto 5 carbon atoms.

[0160] Examples of suitable hydrophobic vinyl comonomers include methylacrylate, ethyl acrylate, propyl acrylate, isopropyl acrylate,cyclohexyl acrylate, 2-ethylhexyl acrylate, methyl meth-acrylate, ethylmethacrylate, propyl methacrylate, vinyl acetate, vinyl propionate,vinyl butyrate, vinyl valerate, styrene, chloroprene, vinyl chloride,vinylidene chloride, acrylonitrile, 1-butene, butadiene,methacrylonitrile, vinyltoluene, vinyl ethyl ether,perfluorohexylethylthio-carbonylaminoethyl methacrylate, isobornylmethacrylate, trifluoroethyl methacrylate, hexa-fluoroisopropylmethacrylate, hexafluorobutyl methacrylate,tris-trimethylsilyloxy-silyl-propyl methacrylate,3-methacryloxypropylpentamethyldisiloxane andbis(methacryloxypropyl)-tetramethyidisiloxane.

[0161] Suitable hydrophilic vinyl comonomers include, without thefollowing being an exhaustive list, hydroxy-substituted lower alkylacrylates and methacrylates, acrylamide, methacrylamide, loweralkylacrylamide and -methacrylamide, ethoxylated acrylates andmethacrylates, hydroxy-substituted lower alkylacrylamides andmethacrylamides, hydroxy-substituted lower alkyl vinyl ethers, sodiumethylenesulfonate, sodium styrenesulfonate,2-acrylamido-2-methylpropanesulfonic acid, N-vinylpyrrole,N-vinylsuccinimide, N-vinylpyrrolidone, 2- or 4-vinylpyridine, acrylicacid, methacrylic acid, amino- (the term “amino” also includingquaternary ammonium), mono-lower alkylamino- or di-loweralkylamino-lower alkyl acrylates and methacrylates, allyl alcohol andthe like. Preferred are, for example, hydroxy-substituted C₂- C₄alkyl(meth)acrylates, five- to seven-membered N-vinyl lactams,N,N-di-C₁-C₄alkyl(meth)-acrylamides and vinylically unsaturatedcarboxylic acids having a total of from 3 to 5 carbon atoms.

[0162] Examples of suitable hydrophilic vinyl comonomers includehydroxyethyl methacrylate, hydroxyethyl acrylate, acrylamide,methacrylamide, dimethylacrylamide, allyl alcohol, vinyl-pyridine,vinylpyrrolidine, glycerol methacrylate,N-(1,1-dimethyl-3-oxobutyl)-acrylamide and the like.

[0163] Preferred hydrophobic vinyl comonomers are methyl methacrylateand vinyl acetate. Preferred hydrophilic vinyl comonomers are2-hydroxyethyl methacylate, N-vinylpyrrolidone and acrylamide. Mostpreferably, the crosslinking of the copolymers of formula (1) is carriedout in the absence of a vinylic comonomer.

[0164] According to another embodiment of the invention, the copolymersof formula (1) are previously converted into an aqueous mesophase whichis at least partly bicontinuous, and the aqueous mesophase is thensubjected to photocrosslinking. A suitable process for producing anaqueous mesophase composition and its crosslinking in an ophthalmicmould is disclosed in PCT application WO 99/12059, which application isherein incorporated by reference. A mesophase of a block copolymer ofthe invention may be prepared, for example, by simply admixing suitableamounts of (i) a prepolymer of formula (1), (ii) an aqueous solutionwhich may comprise, in addition to water, for example a water-misciblesolvent and/or salts, and (iii) optionally further components such as aphotoinitiator, a surfactant a hydrophobic or hydrophilic comonomer asmentioned before, or a pharmaceutical effective agent, for example aprotein, enzyme, vitamin, disinfectant, bactericide or the like, in anyorder at a temperature of, for example, 0 to 100° C., preferably 10 to50° C., and more preferably 15 to 40° C. The mesophases may formspontaneously or upon stirring and/or standing for a suitable period.For example, the components that make up the mesophase are mixed forabout 1 minute to 1 week, preferably for 30 minutes to 5 days and mostpreferably 2 hours to 3 days, in order to form a mesophase which isready for being further processed according to the invention.

[0165] Mesophases of a block copolymer of the invention comprise, forexample, from 10 to 100 percent by weight of block copolymer(s) offormula (1), from about 0 to about 90 percent by weight of aqueoussolution and from 0 to 40 percent by weight of further components.Preferably, the bicontinuous mesophases of a block copolymer of theinvention comprise from about 30 to about 85 percent by weight ofprepolymer(s) of formula (1), from about 15 to about 70 percent byweight of aqueous solution and from 0 to 10 percent by weight of furthercomponents. Particularly preferred mesophases comprise from 30 to 75percent by weight of prepolymer(s) of formula (1) and from 25 to 70percent by weight of aqueous solution.

[0166] The solutions or mesophases comprising a block copolymer offormula (1) may be processed in a manner known per se to form mouldings,especially contact lenses, for example by carrying out thephoto-crosslinking of the prepolymers of the invention in a suitablemould, in particular a contact lens mould. For example, the solution ormesophase is introduced into an opthalmic mould in a manner known perse, such as, especially, by conventional metering in, for example bydropwise introduction or by extrusion. Suitable moulds are generallycustomary contact lens moulds as known in the state of the art. Thus,the contact lenses according to the invention can be manufactured, forexample, in a manner known per se, for example in a conventional“spin-casting mould”, as described, for example, in U.S. Pat. No.3,408,429, or by the so-called Full-Mould process in a static mould, asdescribed, for example, in U.S. Pat. No. 4,347,198. Appropriate mouldsare made, for example, from polypropylene. Quartz, sapphire glass andmetals, for example, are suitable materials for re-usable moulds.

[0167] The crosslinking can be triggered in the mould, for example byactinic radiation, such as, for example, UV light, or by ionisingradiation, such as, for example, gamma radiation, electron radiation orX radiation. The crosslinking can where appropriate also be triggeredthermally or electrochemically. Attention is drawn to the fact that thephotocrosslinking can be carried out in a very short time, for examplein ≦30 minutes, preferably ≦20 minutes, more preferably ≦5 minutes, evenmore preferably in ≦1 minute, especially in 10 to 60 seconds, especiallypreferably, as disclosed in the examples.

[0168] The opening of the mould such that the moulding can be removedfrom the mould can be carried out in a manner known per se.

[0169] The mouldings obtainable from the block copolymers of formula (1)are preferably at least partly bicontinuous, that is to say themouldings have at least two partly bicontinuous phases, for example anoxygen-permeable and an ion-permeable phase, which are intermingled.

[0170] The invention further relates, therefore, to mouldings thatcomprise or, preferably, substantially consist of a crosslinked blockcopolymer of formula (1). Further examples of mouldings of theinvention, apart from contact lenses, are biomedical or specialophthalmic mouldings, e.g. intraocular lenses, artificial cornea, eyedressings, mouldings for use in surgery, such as heart valves,artificial arteries or the like, and films or membranes, e.g. membranesfor controlling diffusion, photo-structurable films for informationstorage, or photoresist materials, e.g. membranes or mouldings for etchresists or screen print resists.

[0171] If the moulding manufactured according to the invention is acontact lens and the latter has been manufactured from a previouslypurified prepolymer using an organic solvent such as an alcohol or anaqueous solution comprising an alcohol or the like, then it is normallyunnecessary for the removal of the moulding to be followed bypurification steps, e.g. extraction, because the prepolymers used do notcontain any undesired low-molecular-weight constituents; consequently,the crosslinked product also is free or substantially free of suchconstituents and subsequent extraction can be dispensed with. Thecontact lens can accordingly be converted into a ready-for-use contactlens directly in conventional manner by hydration. Suitable forms ofhydration capable of producing ready-for-use contact lenses with a widevariety of water contents are known to the person skilled in the art.The contact lens is swelled, for example, in water, in an aqueous saltsolution, especially in an aqueous salt solution having an osmolarity ofapproximately from 200 to 450 milliosmol in 1000 ml (unit: mosm/l),preferably approximately from 250 to 350 mosm/l and especiallyapproximately 300 mosm/l, or in a mixture of water or an aqueous saltsolution with a physiologically tolerable polar organic solvent, forexample glycerol. Swelling of the prepolymer in water or in aqueous saltsolutions is preferred.

[0172] The aqueous salt solutions used for the hydration areadvantageously solutions of physiologically tolerable salts, such asbuffer salts customary in the field of contact lens care, e.g. phosphatesalts, or isotonising agents customary in the field of contact lenscare, such as, especially, alkali metal halides, e.g. sodium chloride,or solutions of mixtures thereof. An example of an especially suitablesalt solution is a synthetic, preferably buffered, lachrymal fluid thathas been matched to natural lachrymal fluid with regard to pH value andosmolarity, e.g. an unbuffered or preferably buffered, for examplephosphate buffer-buffered, sodium chloride solution the osmolarity andpH value of which correspond to the osmolarity and pH value of humanlachrymal fluid.

[0173] The hydration fluids defined above are preferably pure, that isto say free or substantially free of undesired constituents. Mostpreferably, the hydration fluid is pure water or a synthetic lachrymalfluid as described above.

[0174] If the moulding manufactured according to the invention is acontact lens and the latter has been manufactured from an aqueousmesophase of a previously purified prepolymer of the invention, thecrosslinked product also will not contain any troublesome impurities.There is normally no need, therefore, for subsequent extraction. Sincethe crosslinking is carried out in an aqueous medium, there is also noneed for subsequent hydration. In accordance with an advantageousembodiment, therefore, the contact lenses obtainable by this process aredistinguished by the fact that they are suitable for use as intendedwithout extraction or hydration. The expression “use as intended” isunderstood in this context to mean especially that the contact lensescan be inserted into the human eye.

[0175] The copolymers of the invention are especially suitable for themanufacture of mass-produced articles, such as, for example, contactlenses that are worn for a short time, for example for a month, a weekor just one day, and are then replaced by new lenses. This is inparticular because contact lenses prepared from a mesophase of thecopolymers can be used for their intended use without subsequenttreatment steps, such as extraction or hydration.

[0176] In addition, the contact lenses obtainable according to theinvention have a range of unusual and extremely advantageous propertiesand are therefore suited to extended periods of wear (true extendedwear, i.e., seven days or more). Among these properties are, forexample, their excellent compatibility with the human cornea and withtear fluid, if necessary after suitable surface treatment (e.g.coating), which is based on a balanced ratio between water content,oxygen permeability, ion permeability and mechanical and absorptiveproperties. This results in high comfort and the absence of irritationand allergenic effects. Owing to their favourable permeabilityproperties with respect to gases (CO₂ and O₂), various salts, nutrients,water and diverse other components of tear fluid, the contact lensesprepared according to the process of the invention have no effect, orvirtually no effect, on the natural metabolic processes in the cornea.Furthermore, the contact lenses obtainable according to the process areoptical clear and transparent, have a high shelf life and goodmechanical properties, for example concerning the modulus of elasticity,elongation at break or dimensional stability.

[0177] All of the advantages mentioned above apply, of course, not onlyto contact lenses but also to other mouldings of the invention. The sumof the various advantageous aspects in the manufacture of the mouldingsof the invention results in the mouldings of the invention beingespecially suitable as mass-produced articles, such as, for example,contact lenses that are worn for a short period and then replaced by newlenses.

[0178] In the Examples which follow, amounts are by weight, unlessspecified otherwise, and temperatures are given in degrees Celsius.

[0179] Preparation of Telomers of Formula (15)

EXAMPLE 1 Telomer from Mono-2-isocyanatoethyl Methacrylato Trehalose

[0180] A 100 ml three-necked round bottom flask is charged with asolution of 3.8 g (33.4 mmol) cysteamine hydrochloride in 45 ml of 0.1molar aqueous acetic acid. 55 mg (0.2 mmol) α,α′-azodiisobutyramidinedihydrochloride and 53 g (106 mmol) of the monoadduct of IEM toα,α′-trehalose are added. An intensive cooler and an internalthermometer are connected to the flask. The apparatus is evacuated to100 mbar and filled with argon. This is repeated five times.

[0181] The mixture is heated overnight to 60° C. and then cooled to roomtemperature. The product is precipitated in 2 liters of acetone andisolated by filtration, yielding 53.6 g of a slightly yellow coloredpowder. No resonances corresponding to C═C double bonds can be detectedby ¹H-NMR spectroscopy, indicating >98% conversion of the monomer.

[0182] 17.3 g of the product are dissolved in 200 ml water and the pH isadjusted to 10.5 by addition of 107 ml 0.1 molar sodium hydroxidesolution and then diluted with water to a total volume of 500 ml. Saltsand residual low molecular weight components are removed byultrafiltration using a UFP-1-E-4A cartridge from AIG TechnologyCorporation, Needham, Mass., yielding 14.3 g product as retentate and2.5 g permeate of lower molecular weight. The concentration ofamino-groups is determined by functional group titration, result 0.12mmol/g NH₂ corresponding to an average molecular weight of the telomerof 8300 g/mol and a degree of polymerization of 16.

EXAMPLE 2 Telomer from 2-hydroxy-3-methacryloxypropyl TrimethylammoniumChloride

[0183] A 100 mL three-necked round bottom flask is charged with asolution of 0.92 g (10 mmol) thioglycolic acid in 50 mL deionized water.27 mg (0.1 mmol) α,α′-azodiisobutyramidine dihydrochloride and 11.9 g(50 mmol) of 2-Hydroxy-3-methacryloxypropyl trimethylammonium chlorideare added. The pH of the solution is adjusted to pH 3 by addition of 4molar hydrochloric acid. An intensive cooler is connected to the flask.The apparatus is evacuated to 100 mbar and filled with argon. This isrepeated five times. The mixture is heated to 60° C. for three hours andthen cooled to room temperature. An analytical sample is freeze-driedand the monomer conversion is determined by ¹H-NMR spectroscopy. Noresonances corresponding to C═C double bonds can be detected,indicating >98 % conversion of the monomer. The product is isolated byprecipitation of the aqueous solution into 2000 mL acetone. Theprecipitate is filtered off and vacuum dried. Yield 10.2 g white, veryhygroscopic solid. The concentration of carboxylic acid-groups isdetermined by functional group titration, result 0.41 mmol/g COOHcorresponding to an average molecular weight of the telomer of 2440g/mol.

EXAMPLE 3 Oligoethyleneoxide Methacrylate Telomer

[0184] A 250 mL three-necked round bottom flask is charged with asolution of 34 mg (0.125 mmol) α,α′-azodiisobutyramidine dihydrochloridedissolved in 50 mL methanol. 20 g (45.6 mmol) mono-amino terminatedpolyethylene oxide (Blemer® PE 350 from NOF Corporation M_(w)=about 400)and 1.8 g (15.2 mmol) 2-(BOC-amino) ethane thiol are added. An intensivecooler is connected to the flask. The apparatus is evacuated to 100 mbarand filled with argon. This is repeated five times. The mixture isheated overnight to 60° C. and then cooled to room temperature. Ananalytical sample is removed and the solvent evaporated. The monomerconversion is determined by ¹H-NMR spectroscopy. No resonancescorresponding to C═C double bonds can be detected, indicating >98 %conversion of the monomer.

[0185] The product is isolated by evaporation of the solvent. Yield 21 gof a clear, colorless and viscous liquid. The concentration ofBOC-protective groups is determined by titration as 0.34 mmol/g,corresponding to an average molecular weight of the telomer of 2900g/mol. The BOC-protective groups are removed by a treatment of theproduct in an acidic medium.

EXAMPLE 4 N-acryloyl Morpholine/2-hydroxyethyl Acrylamide Co-telomer

[0186] A 1000 mL three-necked round bottom flask is charged with asolution of 28.4 g (250 mmol) cysteamine hydrochloride in 400 mLdeionized water. 407 mg (1.5 mmol) α,α′-azodiiso-butyramidinedihydrochloride and 70.6 g (500 mmol) acryloyl morpholine and 28.8 g(250 mmol) N-hydroxyethyl acrylamide are added. An intensive cooler andan internal thermometer are connected to the flask. The apparatus isevacuated to 100 mbar and filled with argon. This is repeated fivetimes. The mixture is heated to 60° C. for four hours and then cooled toroom temperature. An analytical sample is freeze-dried and the monomerconversion is determined by ¹H-NMR spectroscopy. No resonancescorresponding to C═C double bonds can be detected, indicating >98%conversion of the monomer.

[0187] The remaining mixture is adjusted to pH=10 by addition of 30% KOHsolution. Salts and low molecular weight residues such as unreactedchain transfer agent are removed by reverse osmosis using a MilliporeProscale system equipped with a Millipore Helicon RO-4 Nanomax 50membrane operating at a pressure of 15 bar. The product is isolated fromthe obtained retentate by freeze-drying. Yield: 85 g of a white powder.

[0188] The concentration of amino-groups is determined by functionalgroup titration, result 0.95 mmol/g NH₂ corresponding to an averagemolecular weight of the co-telomer of 1050 g/mol. GPC-analysis indicatesa monomodal molecular weight distribution and the absence of highmolecular weight polymer.

EXAMPLE 5 N-methyl-N-hydroxyethyl Acrylamide/ N,N-dimethyl AcrylamideCotelomer

[0189] A 1000 mL three-necked round bottom flask is charged with asolution of 27.26 g (240 mmol) cysteamine hydrochloride in 400 mLdeionized water. 390 mg (1.2 mmol) 2,2′-azobis-[2-(2-imidazolin-2-yl)propane] dihydrochloride, 42,35 g (427 mmol) freshly distilledN,N-dimethyl acrylamide, and 38,74 g (300 mmol) distilledN-methyl-N-hydroxyethyl acrylamide are added. An intensive cooler and aninternal thermometer are connected to the flask. The apparatus isevacuated to 100 mbar and filled with argon. This is repeated fivetimes. The mixture is heated overnight to 40° C. and then cooled to roomtemperature. An analytical sample was freeze-dried and the monomerconversion was determined by ¹H-NMR spectroscopy. No resonancescorresponding to C═C double bonds could be detected, indicating >98%conversion of the monomer.

[0190] The remaining mixture is diluted with distilled water to 1000 mLtotal volume. Salts and low molecular weight residues such as unreactedchain transfer agent are removed by reverse osmosis using a MilliporeProscale system equipped with a Millipore Helicon RO-4 Nanomax 50membrane operating at a pressure of 10 bar. The product is isolated fromthe obtained retentate by freeze-drying. Yield: 79,1 g of a whitepowder.

[0191] The concentration of amino-groups determined by functional grouptitration indicates an average molecular weight of the co-telomer of 800g/mol. GPC-analysis indicates a monomodal molecular weight distributionand the absence of high molecular weight polymer.

EXAMPLES 6-11 Further Telomers and Co-telomers Are Obtained By theMethod As Outlined in Example 5 Using the Monomers and Chain TransferAgents in a Molar Ratio As Mentioned in the Table Below

[0192] TABLE Weight Chain average Monomer Monomer transfer Molarmolecular Example 1 2 agent ratio weight 6 NHAA — CysHCl 5/—/1 1120g/mol 7 NAM NHAA CysHCl 3/2/1 1280 g/mol 8 NAM NMNHAA CysHCl 2/1/1 1050g/mol 9 NMNHAA — CysHCl 5/—/1 1000 g/mol 10 NAM NMNHAA CysHCl 5/5/2  800g/mol 11 NAM NMNHAA CysHCl 1/4/1  780 g/mol

EXAMPLE 12 Synthesis of a Polydimethylsiloxane with Terminal IsocyanateFunctions

[0193] Under an inert atmosphere, a 750 mL five-necked glass reactorequipped with a glass anchor stirrer, interior thermometer, intensivecooler and a dropping funnel is charged with 8.03 g (36 mmol) distilledisophorone diisocyanate, 80 mg dibutyl tin dilaurate, and 100 mL dryTHF. The homogeneous solution is cooled to −10° C.Hydroxyalkyl-terminated polydimethylsiloxane (Shin-Etsu KF-6003,OH-titration: 0.36 mEq/g) is degassed and dried under vacuum (0.01 mbar)at 70° C. for 30 minutes. After cooling to room temperature, 100 g (36mmol OH-groups) KF-6003 is filled into the dropping funnel and addeddropwise to the diisocyanate solution during 90 minutes, maintaining thesolution temperature at −10° C. The solution is stirred at 0° C. foranother 90 minutes. The solvent is removed on a rotary evaporator at 35°C. Residual solvent is removed under high vacuum (0.002 mbar). Yield:107 g of a clear, colorless and viscous liquid. NCO-titration: 0.31mEq/g (theory 0.33 mEq/g). Hydroxyl-content below detection limit.

EXAMPLE 13 Synthesis of a Block Copolymer of Formula (11)

[0194] Under an inert atmosphere, a 350 mL five-necked glass reactorequipped with a glass anchor stirrer, interior thermometer, intensivecooler and a dropping funnel is charged with 6.2 g (7.75 mmol ammoniumchloride groups) co-telomer of Example 5, 870 mg triethylamine, and 15mL chloroform. After stirring for a few minutes a clear solution isobtained. Two drops (ca. 50 mg) dibutyl tin dilaurate are added. 25 g(7.75 mmol NCO-groups) bis-IPDI-functional polydimethylsiloxane ofExample 12 are dissolved in 25 mL chloroform, filled into the droppingfunnel, and added dropwise to the telomer solution within one hour whilestirring at room temperature. Stirring is continued overnight at roomtemperature. Infrared spectroscopy shows absence of any NCO-absorptionat 2270 cm⁻¹. The polymer is precipitated dropwise into 3.5 liters ofwater under rapid stirring to remove triethylamine and salts. Aftersedimentation of the precipitated material, the liquid is decanted andthe polymer collected and dried under high vacuum (0.01 mbar). Yield:25.9 g white powder. Endgroup titration analysis confirms the absence ofamine and isocyanate groups. Hydroxyl-group content 0.63 mEq/g.

EXAMPLE 14 Synthesis of a Crosslinkable Amphiphilic Block Copolymer ofFormula (1)

[0195] A 100 mL three-necked round bottom flask equipped with a magneticstir bar, internal thermometer, intensive cooler and drying tube, ischarged with 7 g amphiphilic triblock copolymer of Example 13 and 10 mLchloroform. After stirring overnight a clear solution is formed. 460 mg(2.94 mmol) distilled isocyanatoethyl methacrylate (IEM), 18 mg dibutyltin dilaurate and 14 mg triphenyl bismut are added. The solution isstirred overnight at room temperature. Infrared spectroscopyspectroscopy shows absence of any NCO-absorption at 2270 cm⁻¹. Thesolvent is carefully removed on a rotary evaporator and the obtainedmaterial dried under high vacuum (0.01 mbar). Yield: 7.3 g of a clearfilm-forming polymer.

EXAMPLE 15 Casting and Curing of Contact Lenses from a Prepolymer ofFormula (1)

[0196] A centrifugation tube is charged with 4.15 g of product fromExample 14 and 1.04 g n-propanol containing 1.2 weight percent ofphotoinitiator Darocur 2959. The components are thoroughly mixed until ahomogeneous viscous solution is formed. The formulation is centrifugedat 5000 rpm for 10 minutes to remove air bubbles.

[0197] Portions of the formulation are filled into contact lens molds(PP-molds or quartz glass molds) and cured by UV-irradiation for 30seconds with a UV intensity of 1.9 mW/cm² (Macam-lamp). After moldopening perfectly clear and colorless contact lenses are obtained.

[0198] Lenses with an average center thickness of 110 mm show anapparent oxygen permeability of 200 barrers (coulometric method).Mechanical testing shows an E-modulus of 1.6 MPa and elongation at breakabove 100%.

1. A crosslinkable amphiphilic block copolymer of formula

wherein A is a hydrophobic segment selected from the group consisting ofa polysiloxane, a perfluoroalkyl polyether and mixtures thereof, L is isa bivalent linking group of formula-X₁-C(O)—NH-R-NH—C(O)-X₂-  (2a),-X₁-C(O)-R-C(O)-X₂-  (2b),—C(O)-X₂-  (2c),-X₁-C(O)—  (2d)or -X₁-C(O)-X₂-  (2e), wherein X₁ and X₂ are each independently of theother a group —O—, —S— or —NR₁-, R₁ is hydrogen or C₁-C₄-alkyl, R islinear or branched C₁-C₁₈-alkylene or unsubstituted or C₁-C₄-alkyl- orC₁-C₄-alkoxy-substituted C₆-C₁₀-arylene, C₇-C₁₈-aralkylene,C₆-C₁₀-arylene-C₁-C₂-alkylene-C₆-C₁₀-arylene, C₃-C₈-cycloalkylene,C₃-C₈-cycloalkylene-C₁-C₆-alkylene,C₃-C₈-cycloalkylene-C₁-C₂-alkylene-C₃-C₈-cycloalkylene orC₁-C₆-alkylene-C₃-C₈-cycloalkylene-C₁-C₆-alkylene; (alk) isC₂-C₁₂-alkylene; (oligomer) is the radical of a hydrophilic telomerwhich is derived from one or more different copolymerizable vinylmonomers; Q is an organic radical comprising at least one crosslinkableor polymerizable group; m is an integer from 1 to 6, and n is an integer≧1.
 2. An amphiphilic block copolymer according to claim 1, whereinsegment A comprises a polysiloxane block having terminal alkylene groupsof formula

in which (alk′) is alkylene having up to 20 carbon atoms which may beinterrupted by —O—; 80-100% of the radicals R₂, R₂′, R₂″, R₂′″, R₂*, R₃,R₃′ and R₃″, independently of one another, are C₁-C₈-alkyl and 0-20% ofthe radicals R₂, R₂′, R₂″, R₂′″, R₂*, R₃, R₃′ and R₃″, independently ofone another, are C₃-C₁₂-alkenyl, unsubsttituted or C₁-C₄ alkyl- orC₁-C₄- alkoxy-substituted phenyl, fluoro(C₁-C₁₈-alkyl) orcyano(C₁-C₁₂-alkyl), x is 0 or 1, d, is an integer of from 5 to 700, d₂is (n-2) if x is 0, and is n if x is 1 wherein n is as defined above,and the sum of (d₁+d₂) is from 5 to
 700. 3. An amphiphilic blockcopolymer according to claim 1, wherein L is a linking group of formula(2a), wherein R is linear or branched C₆-C₁₀alkylene; orcyclohexylene-methylene or cyclohexylene-methylene-cyclohexylene eachunsubstituted or substituted in the cyclohexyl moiety by from 1 to 3methyl groups.
 4. An amphiphilic block copolymer according to claim 1,wherein the telomer radical-(oligomer)-(Q)_(m) corresponds to formula

wherein B and B′ are each independently of the other a 1,2-ethyleneradical derivable from a copolymerizable vinyl monomer that issubstituted by a hydrophilic substituent by replacing the vinylic doublebond by a single bond, B″ is a 1,2-ethylene radical derivable from acopolymerizable vinyl monomer by replacing the vinylic double bond by asingle bond, Q is an organic radical comprising at least onecrosslinkable or polymerizable group; p and q are each independently ofanother an integer from 0 to 150, wherein the total of (p+q) is aninteger from 2 to 150, u is an integer from 1 to 4, and T is amonovalent group that is suitable to act as a polymerizationchain-reaction terminator.
 5. An amphiphilic block copolymer accordingto claim 4, wherein B and B′ are each independently a radical of formula

wherein R₅ is hydrogen or C₁-C₄-alkyl, and R₆ is a non-ionic substituentselected from the group consisting of C₁-C₂-alkyl, which is substitutedby —OH or —NR₄R₄′, wherein R₄ and R₄′ are each independently of theother hydrogen or C₁-C₂-alkyl; a radical —COOY wherein Y is C₁-C₃-alkyl;C₂-C₄-alkyl which is substituted by —OH, —NR₄R₄′ wherein R₄ and R₄′ areeach independently of another hydrogen or C₁-C₂-alkyl, or Y is a radical—CH₂CH₂—O—(CH₂CH₂O)₂₋₈—H or —C₂-C₄-alkylene-NH—C(O)—O-G wherein —O-G isthe radical of a saccharide; a radical —C(O)—NY₁Y₂, wherein Y₁ and Y₂are each independently of the other hydrogen or C₁-C₆-alkyl which isunsubstituted or substituted by hydroxy, or Y₁ and Y₂ together with theadjacent N-atom form a heterocyclic 6-membered ring having no furtherheteroatom or having one further N- or O-atom; a radical —OY₃, whereinY₃ is hydrogen, C₁-C₄-alkyl which is unsubstituted or substituted by—NH₂ or —N(C₁-C₂-alkyl)₂, or is a group —C(O)C₁-C₂-alkyl; or a 5- or6-membered heteroaromatic or heteroaliphatic radical having one N-atomand in addition no further heteroatom or an additional N-, O- orS-heteroatom, or a 5 to 7-membered lactame.
 6. An amphiphilic blockcopolymer according to claim 5, wherein R₆ is selected from the groupconsisting of a radical —COOY, wherein Y is C₁-C₂-alkyl, C₂-C₃-alkyl,which is substituted by hydroxy, amino or N,N-di-C₁-C₂-alkylamino; aradical —CH₂CH₂—O—(CH₂CH₂O)₂₋₈—H; a radical —C₂-C₄-alkylene-NH—C(O)—O-Gwherein —O-G is the radical of trehalose or a cyclodextrin fragment witha maximum of 8 sugar units; a radical —CO—NY₁Y₂, wherein Y₁ and Y₂ areeach independently of the other hydrogen or C₁-C₄-alkyl which isunsubstituted or substituted by hydroxy, or Y₁ and Y₂ together with theadjacent N-atom form a N—C₁-C₂-alkylpiperazino or morpholino ring; and aheterocyclic radical selected from the group consisting ofN-pyrrolidonyl, 2- or 4-pyridinyl, 2-methylpyridin-5-yl, 2-, 3- oder4-hydroxypyridinyl, N-ε-caprolactamyl, N-imidazolyl,2-methylimidazol-1-yl, N-morpholinyl and 4-N-methylpiperazin-1-yl.
 7. Anamphiphilic block copolymer according to claim 1, wherein Q is a radicalof the formula -(R₁₁)_(t)-X-Q₁  (7), wherein R₁₁ is C₁-C₈-alkylene; oris a radical of formula—C(O)-X₃-Alk-,  (8a),—C(O)—O-Alk′-NH—C(O)—O—(CH₂CH₂O)₉—CH₂CH₂-  (8b), or—C(O)—O-Alk′-NH—C(O)—O-G₁-  (8c),Alk is C₂-C₁₂-alkylene which isunsubstituted or substituted by hydroxy or a radical —N(R₁₂)₃ ⁺An-wherein R₁₂ is hydrogen or C₁-C₄-alkyl and An⁻ is an anion, Alk′ isC₂-C₁₂-alkylene, X₃ is —O— or —NR₁₃-, R₁₃ is hydrogen or C₁-C₄-alkyl, tis an integer of 0 or 1, g is an integer from 1 to 23, G₁ is the radicalof a saccharide reduced by one hydroxy group; X is a group —O—, —S—,—NR₁₃′- or —N(R₁₃′)₂ ⁺-An⁻ wherein R₁₃′ is hydrogen or C₁-C₄-alkyl andAn⁻ is an anion, Q₁ is a radical R₁₄ or is a radical of formula

(Alk″) is linear or branched C₃-C₆-alkylene, (Alk*) is linear orbranched C₁-C₆-alkylene, (Alk**) is linear or branched C₂-C₁₂-alkylene,and R₁₄ is a radical of formula

wherein R₁₇ is hydrogen, C₁-C₄-alkyl or halogen, and each of R₁₅ and R₁₆independently of the other is hydrogen, C₁-C₄-alkyl, phenyl, carboxy orhalogen.
 8. An amphiphilic block copolymer according to claim 7 whereint is 1, X is —O— or —NH—, and R₁₁ is methylene; or is a radical offormula (8a), wherein (Alk) is C₂-C₄-alkylene, and X₃ is —O—, —NH— or—N(C₁-C₂-alkyl)-; or is a radical of formula (8b) wherein (Alk′) isC₂-C₄-alkylene, and g is an integer of from 1 to 3; or is a radical offormula (8c) wherein (Alk′) is C₂-C₄-alkylene, and —OG₁ is the radicalof trehalose or a cyclodextrin fragment with a maximum of 8 sugar units,each reduced by one hydroxy group.
 9. An amphiphilic block copolymeraccording to claim 7, wherein Q₁ is a radical R₁₄ of formula (10) or aradical of formulae (9a), (9b) or (9c), wherein -[(Alk″)-OH]— is2-hydroxy-1,3-propylene, (Alk*) is C₁-C₃-alkylene, (Alk**) isC₂-C₄-alkylene, R₁₅ and R₁₆ are each hydrogen, and R₁₇ is hydrogen ormethyl.
 10. An amphiphilic block copolymer according to claim 1 offormula

wherein A is a hydrophobic polysiloxane segment, L is a linking group offormula (2a), wherein R is linear or branched C₆-C₁₀alkylene;cyclo-hexylene-methylene or cyclohexylene-methylene-cyclohexylene eachunsubstituted or substituted in the cyclohexyl moiety by from 1 to 3methyl groups; or phenylene or phenylene-methylene-phenylene eachunsubstituted or substituted in the phenyl moiety by methyl; (alk) isC₂-C₄-alkylene; R₅, R5′ and R₅″ are each independently of the otherhydrogen or methyl; R₆ and R₆′ are each independently of the otherselected from the group consisting of a radical —COOY, wherein Y isC₁-C₂-alkyl, C₂-C₃-alkyl, which is substituted by hydroxy, amino orN,N-di-C₁-C₂-alkylamino; a radical —CH₂CH₂—O—(CH₂CH₂O)₂₋₈—H; a radical—C₂-C₄-alkylene-NH—C(O)—O-G wherein —O-G- is the radical of trehalose ora cyclodextrin fragment with a maximum of 8 sugar units each reduced byone hydroxy group; a radical —CO—NY₁Y₂, wherein Y₁ and Y₂ are eachindependently of the other hydrogen or C₁-C₄-alkyl which isunsubstituted or substituted by hydroxy, or Y₁ and Y₂ together with theadjacent N-atom form a N—C₁-C₂-alkylpiperazino or morpholino ring; and aheterocyclic radical selected from the group consisting ofN-pyrrolidonyl, 2- or 4-pyridinyl, 2-methylpyridin-5-yl, 2-, 3- oder4-hydroxypyridinyl, N-ε-caprolactamyl, N-imidazolyl,2-methylimidazol-1-yl, N-morpholinyl and 4-N-methylpiperazin-1-yl; t is1 and R₁₁ is methylene; or a radical of formula —C(O)-X₃-Alk-,  (8a),—C(O)—O-Alk′-NH—C(O)—O—(CH₂CH₂O)—CH₂CH₂—  (8b), or—C(O)—O-Alk′-NH—C(O)—O-G₁-  (8c), wherein (Alk) and (Alk′) are eachindependently of the other C₂-C₄-alkylene, X₃ is —O—, —NH— or—N(C₁-C₂-alkyl)-, g is an integer of from 1 to 3, and —OG₁- is theradical of trehalose or a cyclodextrin fragment with a maximum of 8sugar units each reduced by one hydroxy group, X is —O— or —NH—, Q₁ is aradical of formula

T is a monovalent group that is suitable to act as a polymerizationchain-reaction terminator, u is a number from 1 to 2, p and q are eachindependently of the other an integer from 0 to 99 wherein the sum of(p+q) is an integer from 3 to 99, and n is an integer from 2 to
 8. 11. Aprocess for the manufacture of a moulding, which comprises crosslinkingan amphiphilic block copolymer of formula (1) according to claim 1 in amould.
 12. A process according to claim 11 wherein the moulding is anophthalmic moulding and wherein the block copolymer is photo-crosslinkedin an ophthalmic mould using actinic radiation.
 13. A mouldingobtainable by the process according to claim
 11. 14. A mouldingaccording to claim 13, which is an ophthalmic moulding.
 15. An oligomerof formula

wherein X₄ is —SH, —NHR₁, carboxy or a carboxy derivative, (alk) isC₂-C₁₂-alkylene, B and B′ are each independently of the other a1,2-ethylene radical derivable from a copolymerizable vinyl monomer thatis substituted by a hydrophilic substituent by replacing the vinylicdouble bond by a single bond, B″ is a 1,2-ethylene radical derivablefrom a copolymerizable vinyl monomer by replacing the vinylic doublebond by a single bond, Q is an organic radical comprising at least onecrosslinkable or polymerizable group; p and q are each independently ofanother an integer from 0 to 150, wherein the total of (p+q) is aninteger from 2 to 150, u is an integer from 1 to 4, T is a monovalentgroup that is suitable to act as a polymerization chain-reactionterminator, R₁₁ is C₁-C₈-alkylene; or is a radical of formula—C(O)-X₃-Alk-,  (8a),—C(O)—O-Alk′-NH—C(O)—O—(CH₂CH₂O)₉—CH₂CH₂—  (8b), or—C(O)—O-Alk′-NH—C(O)—O-G₁-  (8c), wherein Alk is C₂-C₁₂-alkylene whichis unsubstituted or substituted by hydroxy or a radical —N(R₁₂)₃ ⁺An-,R₁₂ is hydrogen or C₁-C₄-alkyl, An⁻ is an anion, Alk′ isC₂-C₁₂-alkylene, X₃ is —O— or —NR₁₃-, R₁₃ is hydrogen or C₁-C₄-alkyl, gis an integer from 1 to 23, G₁ is the radical of a saccharide reduced byone hydroxy group, t is an integer of 0 or 1, and X is a group —O—, —S—,—NR₁₃′- or —N(R₁₃′)₂ ⁺- An⁻ wherein R₁₃′ is hydrogen or C₁-C₄-alkyl andAn⁻ is an anion.